Peanut Immunotherapy Update: Aimmune Therapeutics
At last weekend’s annual scientific meeting of the American Academy of Allergy, Asthma & Immunology, Aimmune Therapeutics and DBV Technologies presented updates on the two immunotherapy approaches for peanut allergy that have progressed farthest in the U.S. Food and Drug Administration’s approval process for bringing new drugs to market. Here we present findings released by Aimmune Therapeutics; tomorrow, we’ll feature research recently published by DBV Technologies.
In December 2018, Aimmune submitted a Biologics License Application to FDA for AR101, a standardized peanut oral immunotherapy product, for treatment of peanut allergy in children ages 4 to 17. Among the AR101 presentations given at AAAAI 2019 were supplemental findings from the phase 3 PALISADE trial, which enrolled nearly 500 patients ages 4 to 17, as well as analysis from a follow-on trial to PALISADE.
In the PALISADE trial, discussed in detail in a 2018 FARE Blog post, 372 children and adolescents received the active AR101 treatment, while 124 received placebo. Following a year of treatment, gradually up-dosing to a daily maintenance dose, 67 percent of the children who started treatment with AR101 – and 85 percent of those who completed the active treatment – could tolerate eating at least 600 mg of peanut protein (approximately two peanut kernels), compared to 4 percent of children who received a peanut-free placebo. At AAAAI 2019, further analysis was reported that, compared to placebo patients, AR101-treated patients who completed the exit food challenge were 95 percent more likely to tolerate any peanut protein challenge dose.
Throughout the trial, fewer AR101-treated patients experienced accidental peanut exposures requiring treatment than did placebo patients, 6.5 percent versus 10.5 percent. While none of the AR101-treated patients required epinephrine for an accidental peanut exposure, 2.4 percent of the placebo group had accidental peanut exposure resulting in a severe allergic reaction that required epinephrine. During the second half of the year-long course of treatment, the fraction of AR101-treated patients who reacted to an accidental peanut exposure declined by 70 percent.
AR101-treated patients also reported fewer accidental exposure reactions to non-peanut food allergens than did placebo patients. Over the full length of the PALISADE trial, 22.6 percent of placebo patients experienced accidental exposure to a food other than peanut, compared to only 13.4 percent of AR101-treated patients. This difference was more pronounced in the second six months of treatment, during which 15.3 percent of the placebo group – but only 7.4 percent of the AR101-treated group – reacted accidentally to a non-peanut food allergen.
Finally, an open-label follow-on trial to PALISADE, called ARC004, found that ongoing daily 300-mg AR101 dosing resulted in increased peanut tolerance above the levels achieved during the one-year PALISADE trial. Among those AR101-treated patients who tolerated less than a 1,000-mg single dose at the PALISADE exit challenge, nearly two-thirds were able to tolerate more peanut protein at another challenge 28 weeks later. Moreover, half of the AR101-treated patients taking a daily therapeutic dose were able to tolerate a 2,000-mg single dose, that is, double the highest dose administered in the PALISADE trial.